Sodium Iodide → N-({4-[4-(4-pyrrolidin-1-ylbutoxy)phenyl]tetrahydro-2H-pyran-4-yl}methyl)pyridin-2-amine

HRID 273039Notes

Reaction equation

HRID 273039 reaction equation
Cl[CH2:2][CH2:3][CH2:4][CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2([CH2:19][NH:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=3)[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)=[CH:9][CH:8]=1.[NH:27]1[CH2:31][CH2:30][CH2:29][CH2:28]1.C(=O)([O-])[O-].[Na+].[Na+].[I-].[Na+]>C(O)CCC>[N:27]1([CH2:2][CH2:3][CH2:4][CH2:5][O:6][C:7]2[CH:12]=[CH:11][C:10]([C:13]3([CH2:19][NH:20][C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=4)[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[CH:9][CH:8]=2)[CH2:31][CH2:30][CH2:29][CH2:28]1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 10340Sodium CarbonateHCID 31268PyrrolidineHCID 68576502N-({4-[4-(4-chlorobutoxy)phenyl]tetrahydro-2H-pyran-4-yl}methyl)pyridin-2-amine

Product 1

HCID 59837489N-({4-[4-(4-pyrrolidin-1-ylbutoxy)phenyl]tetrahydro-2H-pyran-4-yl}methyl)pyridin-2-amineYield 29%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Procedure

A mixture of N-({4-[4-(4-chlorobutoxy)phenyl]tetrahydro-2H-pyran-4-yl}methyl)pyridin-2-amine (180 mg, 0.481 mmol), pyrrolidine (80 μl, 0.963 mmol), sodium carbonate (102 mg, 0.963 mmol) and sodium iodide (4 mg, 0.024 mmol) were stirred in butanol (5 ml) at 100° C. for 24 hours until complete. Butanol was removed in vacuo and the residue partitioned between ethyl acetate (40 ml) and water (40 ml). Organic layer was dried over sodium sulphate, filtered and concentrated in vacuo to give a brown solid. Solid was purified by flash chromatography on silica gel eluting with dichloromethane:methanol:ammonia (98:2:02 to 96:4:0.4 by volume), followed by recrystallisation from ether (1.5 ml) to give the title compound (56.6 mg, 29%). 1H NMR (400 MHz, CDCl3) δ 1.78-2.00 (m, 12H), 2.08-2.20 (m, 2H), 2.54-2.90 (m, 4H), 3.50 (d, 2H), 2.54-2.63 (m, 2H), 3.79-3.88 (m, 2H), 3.96-4.08 (m, 2H), 6.23 (d, 1H), 6.50 (t, 1H), 6.90 (d, 2H), 7.25 (d, 2H), 7.32 (t, 1H), 8.01 (d, 1H). LRMS APCI+ m/z 410 [MH]+.

Workup

  1. customButanol was removed in vacuo
  2. customthe residue partitioned between ethyl acetate (40 ml) and water (40 ml)
  3. dry with materialOrganic layer was dried over sodium sulphate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto give a brown solid
  7. customSolid was purified by flash chromatography on silica gel eluting with dichloromethane:methanol:ammonia (98:2:02 to 96:4:0.4 by volume)
  8. customfollowed by recrystallisation from ether (1.5 ml)

Sources & evidence

ORD record
ord-037c6caaf1da4a208977c10089a452e0
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

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